Low Carb Diets and Testosterone

This post is geared to an elite group of readers: Men on LC (low carb) or VLCK (very low carb/ketogenic) diets who engage in moderate to heavy weightlifting on a regular basis. I’ll go a step further and assume they are concerned about boosting their testosterone levels. Testosterone after all, is a pretty important factor in muscle development.

Prior to any research into this topic, my gut feeling was that restrictive diets – low carb in particular – would have negative consequences for testosterone. The rationale for this line of thinking is that restriction of carbohydrates would signal to the body that hard times we’re being experienced and that reproductive functions should be put on hold until more flush times returned. Since women have a greater energy investment in reproductive functions, I would expect that LC and VLCK diets to have even greater effects on female hormones, but that’s a topic for another time. It’s enough just to consider male sex hormones for now.

Let’s see what the research has to say on this matter.

The top Google search results for low carb testosterone bring up sites run by and geared to “roid boys” and muscle heads (bro scientists) [1,2,3]. And for the record, let me say some of it is damn good and quite informative. For a very succinct, straightforward and slickly presented post on this subject see the article from Testosterone Nation reference above.

Winner! Winner! Steak Dinner!

Bottom line: it doesn’t look good for testosterone levels with respect to weightlifting while eating LC and VLCK. However, there is a glimmer of hope if the carbs that are allowed, are properly timed.

In a study out of the University of North Carolina, 20 endurance athletes were divided into two groups [4]. One was put on a “low carb diet” the other on a “normal carb diet” and then put on 3 days of intensive training. Blood samples were taken over the course of the experiment and analyzed for free testosterone and cortisol. The low carb group’s diet was only defined as 30% of daily intake, which is not very low carb by most standards and the other group referred to as “control carbohydrate” was 60% of daily intake. I know some would have problems with listing carbs as a % of daily intake and not absolute amounts.

I have other problems with the diet regimens in this study.

The subjects prepared their own meals with suggestions about what to consume and kept a log of their diet. But this highlights why human subjects are difficult beasts to do diet research on. After all, you can’t keep them in a cage and feed them human chow pellets. The best you can do for human diet studies is employ a metabolic ward, but this is expensive and restrictive and as such, can only last for a relatively short study period. I often wonder why not employ prepared packaged meals much like Weight Watchers or Atkins microwave meals.

However, the most egregious is that when the subjects were at the research training facility during the training phase, they were supplemented with Polycose, which consists solely of glucose polymers derived from cornstarch, with 87.5 grams of carbs for the normal carb group. Boost High Protein Drink for the low carb group. Good lord! The ingredients in Boost High Protein Drink in order are water, sugar, corn syrup, milk protein concentrate, vegetable oil, soy protein, vitamins and minerals with 33 grams of carbohydrates, 23 grams coming from simple sugars and 45 grams of protein.

You would think in the one situation where the researchers had some control over carbohydrate intake they would have done a better job. They probably got a good deal on Boost at the local CVS. Here’s an idea: since Polycose is a powder that you mix in water why not supplement the low carb group with whatever was needed with 45g of protein powder in water?

Data Massaging FTW!

While this study is cited in the some of the roid blogs mentioned above, the results are weak in my opinion. There seems to be a general trend of lower free testosterone in the low carb group but it is not significant. There was a significant increase in cortisol levels in the low carb group, however, 24.1 vs 27.6 ug/dl. The authors resort to some statistical contortions to get a significant result for the free testosterone to cortisol level.

Nevertheless, due to these trends toward differing responses in and between the groups, an analysis of covariance (ANCOVA) was also conducted on the fTC ratio in which the initial resting Pre 1 levels of the ratio for each group were used as covariates. This alternative analysis revealed a significant group by time interaction effect for the fTC ratio change.

The authors strategically place in the abstract the dramatic result of 43% significant reduction in the free testosterone ratio to cortisol in the low carb group, using the aforementioned massaging of the data then presenting it as a percentage. In fact, these are percentages of percentages. See why percentages can be misleading. The absolute numbers are way less impressive 1.53 vs 0.82.

I’m nit-picking this study because it is the one making the most rounds from bloggers who most probably only have an abstract available and only see the 43% reduction number.

“You’re Overtraining Son.”

I did find it interesting that the researchers proposed using the free testosterone to cortisol ratio as a measure of overtraining. It would be nice to have a quantitative value for overtraining rather than subjective one of some muscle head walking by you at the gym declaring that you’re overtraining.

In another study [5] seven healthy men were first put on a high-carb and then a high-protein diet. I only have the abstract, so have no idea as to the actual composition of carbs of each diet other than total calories and fat content were kept equal in both treatments, however, absolute values are provided for the measured testosterone and cortisol. Testosterone was significantly higher after 10 days on the high carb diet than the protein diet (468 +/- 34 ng/dl) vs (371 +/- 23 ng/dl). Cortisol levels were consistently lower in the high carb group after 10 days (7.74 +/- 0.71 micrograms/dl) vs (10.6 +/- 0.4 micrograms/dl ).

Feeling Stressed Out?

The astute reader will notice besides testosterone, cortisol was measured in these studies. We all have heard of cortisol, “the stress hormone”, from mainstream media and supplement manufacturers hawking their latest “cortisol blockers.”

The research would suggest that low carb diets raise cortisol levels [6]. Cortisol in turn, has negative influence on testosterone and is why it must be discussed [7, 8].

Gotta Lift Big to Get Big

Exercise in general, temporarily raises cortisol and testosterone levels. So the goal of the bodybuilder in his training is optimize for the greatest testosterone and least cortisol release. When glycogen stores in the liver and muscles are depleted during a weightlifting session, cortisol is called upon to breakdown muscle for amino acids to create glucose and glycogen in the liver. So ideally, we want to go into the gym with as much glycogen as possible. This is the rationale behind carb-loading.

Hopefully you see where this is going for LCers and especially VLCKers. Since they’re showing up at the gym with low glycogen from the get go, cortisol will rise earlier and to a higher level during and after training in their bodies.

Testosterone = Winning!

While most of the research shows only a negative correlation between testosterone and cortisol and not a causative one, there is some evidence to suggest a causative effect [7, 8, 9]. One fascinating piece of research out of The University of Texas at Austin would suggest that cortisol not only affects testosterone levels, but also how we respond to it behaviorally [10]. Think of the ultra-competitive juicer or roid rage. Apparently, cortisol blunts the behavioral effects of testosterone.

The study looked at 57 participants in a one-on-one competition. The cortisol and testosterone levels were looked at before and after competition in both the winners and losers. The losers were given a chance at a rematch if they desired. The losers who had high-testosterone/low-cortisol all agreed to a rematch. Those with a low-testosterone/high-cortisol all declined the offer of a rematch.

You Can’t Out Flex a Hungry Tiger

The author of the UT fluff piece for the study suggests that this makes sense from an evolutionary perspective. If one is in a fight-or-flight stress situation then there is no time for such things as competitive posturing or mating behavior or in the previous study, returning to the gym. No amount of flexing out or posturing is going to save your ass from a saber-tooth tiger.

One last aspect to look at regarding low carbs and testosterone lies with the brain. The brain is constantly monitoring blood glucose levels through the hypothalamus. There is evidence to suggest that a hormone released from the hypothalamus called Gonadotropin Releasing Hormone (GnRH) is inhibited under low glucose conditions [11]. GnRH, through a cascade of biochemical events, influences the testes to produce testosterone.

Time Your Carbs Around Your Workouts

Okay, what can LC and VLCK folks do, if anything, from being a stressed-out wimp at the gym?

The author of the post at Testosterone Nation has some excellent strategies. His name is Brad Dieter and here are his suggestions.

Time your carbs. Low Carbers are allowed some carbs, so eat these prior to your workout. He didn’t say anything about immediately following a workout, but I would recommend consuming some carbs post-workout as well.

Second, increase your protein content so amino acids can be used for gluconeogenesis to reduce cortisol.

One final note and caution: don’t come away from this with this thinking that more carbs equals more testosterone. Excessive carb intake is associated with low testosterone [12].

Photo Credits (morguefile.com):

Steak: kconners

Massage: Yoel

defeat: marykbaird

stress: pedrojperez

weights: cohdra

winners: GaborfromHungary

tiger: watchthebirdy

bread: agathabrown

pie: alcine

Are Phytosome Herbal Extracts Worth It?

Recently, while shopping at my local nutritional supplements store, I was faced with a dilemma: should I shell out more money for an herbal extract that was prepared using the patented phytosome technology or opt for the considerably cheaper regular extract? I then was made to recall an incident at the same store concerning a very similar quandary.

I overheard a woman loudly exclaim, “It’s a no-brainer!” while grabbing the large, cheap bottle of raw herb when confronted with the higher price tag on the more refined herbal extracts in the smaller bottles. Whenever I hear that expression I reflexively cringe and immediately become wary. My supplement store dilemma, along with this unpleasant memory, initiated an investigation into phytosome-prepared herbal extracts. I sincerely hope you will find the results of my investigation beneficial in your own herbal supplements shopping.

Let’s breakdown the word phytosome: phyto=plant, some=cell. “Plant-cell” you say, well no. “Phyto” here refers to the plant constituent that is the target of an herbal extract. For example, my dilemma was brought about by the herbal extract of hawthorn (pictured above in the lead image of this post). Vitexin is thought to be the active ingredient in hawthorn, responsible for its reputed heart and cardiovascular health effects and is the phyto in this case [1]. The some or cell part of the preparation is created using phosphotidylcholine and is the same for all phytosome preparations.

The phospholipid – phosphatidylcholine – contains two unique parts to its structure: one part is hydrophilic or “water-loving” and the other part is hydrophobic or “water-hating.” What this all boils down to is that these phospholipid molecules will assemble themselves into a cell-like membrane and structure when placed in water. Think of a red blood cell and the hemoglobin contained within. The vitexin in our case is chemically bonded to the choline head group of the phospholipid. The only way “to get the picture” is to get the picture. A picture is indeed worth a thousand words – seriously, click on the reference link.

Let’s look at the schematic more closely [2]. Those things that look like tadpoles with two tails are the phosphotidylcholine molecules. The triangles inside the tadpole head are the phytos, and in our case, represent the vitexin molecules.

The schematic also addresses another issue that needs clarification. The top half is labeled as a liposome. This differs from a phytosome in that the extracted plant chemicals are floating freely in the liquid center. Some readers may be familiar with the liposomes used in the cosmetics industry in lotions and creams to deliver substances to the skin. We will shortly see why this distinction is important. Hint: compare the number of triangles to double-tailed tadpoles in the top (liposome) to the bottom (phytosome) parts in the previously referenced schematic.

So why go through all this trouble to prepare a herbal extract as a phytosome preparation?

Phytosomes are used mainly for herbal extracts containing polyphenols which are water soluble. Vitexin is a type of polyphenol. Large water soluble substances are poorly absorbed through the intestinal lining and phytosomes present a way to overcome this by enclosing these substances in a lipid soluble structure [3].

There is also the other problem of the active compound being destroyed by the harsh environment of the stomach and its gastric juices before even reaching the intestine. Incorporation of the extract into the phytosome protects it [3, 4].

I thought by doing this post it would provide a respite from mentioning gut bacteria, but it seems there is no rest for the weary. Some gut bacteria will “eat” polyphenols that make it to the intestine. In some cases, this might not be entirely bad as the byproducts of bacteria consumption may have their own health benefits [5]. So packaging of an extract as a phytosome would prevent it from being available to bacterial degradation.

Furthermore, the chemical bonding of the plant compound to a phoshotidylcholine molecule in a phytosome provides greater stability and protection than the freely-floating compound within the liquid center of a liposome and allows for greater packaging of the compound than a liposome [6].

I recently watched the movie Troy and this suggested an analogy: packaging phytonutrients in a phytosome is like packaging Greek warriors in a Trojan horse. In the former to make it through the intestinal wall to the bloodstream intact and in the latter to make it from the beach and then through the Trojan Wall intact.

So what exactly is the evidence that phytosome preparations provide better absorption over regular extracts?

In many cases, it’s indirect. Parameters associated with an herbal supplement, say lipid profiles, were found to be positively affected by phytosome preparations and superior over regular extracts [7]. However, no attempts were made at measuring the actual appearance in the bloodstream.

One study looking at the uptake of a component of milk thistle from a phytosome and non-phytosome preparation was studied in gall bladder surgery patients [7]. The appearance of the active ingredient in the bile was measured and it was found that the phytosome preparation was superior over the regular extract with four times greater passage through the liver for the phytosome version.

Another study where human subjects were given phytosome silibinin or regular silymarin extract found seven times greater plasma levels of silbinin with the phytosome preparation [7]. I do have a problem with this study however; the phytosome preparation used pure silibinin which is one component of silymarin extract. This particular study used an amount of silymarin that had the equivalent amount of silbinin of the phytosome preparation to overcome this discrepancy. For a proper control, a non-phytosome, pure silibinin extract should have been used. The devil is often in the details (methods) of a scientific study.

In a Gingko biloba study 2 to 4 times greater plasma concentration of terpenes was achieved over non-phytosome preparation.

In a green tea polyphenols study plasma concentrations of polyphenols more than doubled over non-phytosome preparation.

Unfortunately, I could not find studies on hawthorn phtyosome and plasma levels. Phtyosome research for now seems to be focused on milk thistle, green teapolyphenols, grapeseed extracts, and gingko biloba.

Okay, so what about just taking more of the cheaper variety to compensate for its lesser bioavailability, which the lady in the supplements store proclaimed as a no-brainer? The price of my hawthorn regular extract is $5 for 120 capsules of 250 mg extract standardized to 1.8% “hyperosides” while the phytosome is $20 for 60 capsules of 300 mg of 3% vitexin standardized extract.

First, we are confronted with the problem that one extract is standardized to 1.8% “hyperosides” while the other is standardized to 3% vitexin. Hmm, okay. I’m putting “hyperosides” in quotes because hyperoside is a specific compound and not a group of compounds, as in say polyphenols, so don’t know why it appears in the plural form on the label. If you look at the molecular structure of the two they are pretty damn close, differing by only a hydroxyl group. But in the world of biochemistry, any minor change in a molecule can have a huge biological effect. Methamphetamine and pseudoephedrine vary by only one measly hydroxyl group – just ask Walter White or perhaps Jessie. “Science, bitch!”

However, these are relatively crude extracts and since vitexin is present in greater amounts than hyperoside in the leaves and flowers and would be co-extracted with hyperoside the non-phytosome extract may have similar levels of vitexin as the phytosome extract [8].

For simplicity’s sake, we will say both have similar amounts of active ingredient, capsule for capsule. If we were seeing four to seven times greater absorption we would need to take four to seven times more of the regular extract. Let’s go with the lower ratio of 4 times. This would work out to saving approximately ten dollars if we were to quadruple the dose of the regular extract. It should be noted that it may be naive to assume taking more of the regular extract can overcome this difference in absorption.

I’ve made some pretty liberal assumptions in the above calculations to get to a point. The pharmaceutical industry knows that people in general don’t relish taking pills and they go to great lengths to devise formulations to reduce the number of pills one has to take. I know, I don’t enjoy choking down a bunch of pills, so we must also consider intangible factors.

Furthermore, we may be unwittingly ingesting more unwanted compounds by increasing the number of pills taken of an extract. Plants can contain heavy metals, pesticides, or even co-occurring toxic compounds. Crude extracts could very well concentrate these undesirables, so less of an extract taken is probably better in the long run.

However, there is a much greater consideration.

The aforementioned studies often found that not only were the phytosome compounds better absorbed, but they also stayed in the bloodstream longer. Therefore, we not only have to take more of the regular extract, but also we need to keep re-dosing to compensate for the more rapid clearance of the non-phytosome preparation. This would also suggest that the phytosome is protecting the compound in the bloodstream from being degraded and thereby aiding in getting it to the site within the body where it’s being targeted.

Finally, if the compound needs to affect its action inside the cell then it would exhibit the same barriers to getting through the intestinal lumen as through the cell membrane. This barrier could potentially be overcome by a phytosome prep.

Bottom line: I’ve convinced myself that the phytosome preparation is the one for me — it’s a genuine “no brainer.” But I may have to start a cloud-funding campaign to purchase it!

Photo Credits (morguefile.com):

Hawthorn Berries: GaborfromHungary

Tadpole: AcrylicArtist

No Entry: hotblack

Pinata: krosseel

Greek Soldier: mensati

Corroded Surface: andyk

Brain: Yoel (red x added by me)

Butyrate and Low Carb Diets

In my posts thus far, there is a character lurking in the wings. This mysterious character comes in the form of a rather simple, nondescript molecule consisting of only four carbons, eight hydrogens and two oxygen atoms. It belongs to a class of chemicals called short chain fatty acids or SCFAs. Oh, and it gives vomit its characteristic smell – gotta love Wikipedia for such facts! Give up? If you guessed butyrate, you would be correct.

This seemingly simple molecule has been shown to have a complex range of actions in “test-tube/Petri plate” and whole organism studies for both humans and mice. It has a wide range of implications for colonic health, glucose and insulin regulation, as well as for weight-loss.

Butyrate is produced in the colon mainly through the bacterial fermentation of non-starch polysaccharides and resistant starch (RS). The production of butyrate will in a large part be dependent on the dietary intake of foods containing fiber, e.g. fruits and vegetables. This may be a concern for those on a low-carb diet since the raw material (fiber) for butyrate production is being restricted.

There are several studies in obese humans showing that fecal butyrate and butyrate-producing bacteria are reduced on low-carb diets [1,2,3]. Why should this be of concern? Well, colonic cells prefer to use butyrate as an energy source. In mice, colonic epithelial cell atrophy can be induced by a no-fiber diet, and to some degree, prevented, by butyrate colonic infusion [4,5]. In other words, adding butyrate via fiber consumption can benefit the cells lining the walls of your colon.

The human studies referenced above involved measuring the butyrate levels of the subjects’ feces. You can feel for the research subjects having the ignominy of being put on a restricted diet and then having to collect their stools in a plastic bag. Not fun. Sympathies also go out to the research assistants tasked with pureeing the stool samples. Not fun x2!

What kept nagging at me was whether fecal butyrate levels were indicative of the actual levels in the colon. After all, given that 95% of the butyrate produced in the colon is absorbed and utilized by the colonic epithelial cells for energy, then very little should appear in the feces. At least one would surmise.

It was very refreshing to find a blog post along this same line of thought. The writer suggests that the reduced butyrate levels in the feces in the low carb situation can just as likely be explained as a greater absorption in the colon. However, unlike in experimental cows where a port can be surgically implanted into the rumen, fecal sampling is the best non-invasive tool for measuring butyrate in humans.

Rich reviewed the movie Food, Inc. awhile back. There is a scene where a researcher is being interviewed next to a cow with just such a port [6]. He reaches into the port and pulls out some of the contents. If I remember correctly, he was trying to associate the emergence of deadly E. coli O157:H7 in cows with corn feeding as opposed to grass-fed cattle. He hypothesized this was due to the unfavorable changes in the gut biome.

Regarding the topic of gut biome, there are certain species of bacteria in the colon that are good at turning fiber and resistant starch into butyrate. These bacteria seem to thrive on such things as inulin, psyllium, RS, and fructo-oligosaccharides. I know that Rich supplements his low carb diet with a glass or two of Metamucil, which contains psyllium husks as its primary soluble fiber ingredient (70% soluble fiber, 30% insoluble fiber). I think that some low carbers are too restrictive and forget that not all plant-based carbs are equal. Some are necessary for gut health and have a very low glycemic index.

Thanks for mentioning my Metamucil supplementation, Rob 😉 I use it primarily to smooth the elimination process. Even with a higher carb diet, it’s still difficult to ingest sufficient soluble fiber to facilitate things and it’s twice as difficult when you’re older. Hence, a fiber supplement to the rescue. I mix a level teaspoon of Metamucil with a scoop of creatine powder prior to cooking breakfast. It’s a refreshing concoction and the orange-flavored (sugar-free variety) provides a tasty vehicle for the flavorless creatine powder. If I’m experiencing benefits beyond smoother elimination such as lowering cholesterol, better glucose control, and healthier and happier gut microbiota, so much the better!

In reviewing studies, both mouse and human, there seems to be no real consistency in the type of carbs or control for type and amount of fiber and resistant starch used for the experimental low-carb regimen other than it limits carbs to around 25g per day. This places such a diet within the ketogenic range.

Butyrate may also be important to the low carber since there is some evidence (mouse and test-tube) that it influences the production of a certain satiety hormone, signaling fullness, as well as a metabolic hormone that lowers blood glucose [7,8].

Much attention, both mainstream and academic, has focused on the role of butyrate on colon cancer.

In the test tube, butyrate is capable of interacting with the colonic cell’s DNA to influence such things as cell division, growth, differentiation, and death. All these have implications for both cancer prevention and promotion. The review article, “Does Butyrate Protect from Colorectal Cancer?” showed mixed results in animal models [9]. One problem with these studies is being able to know whether the butyrate administered managed to get to targeted cells in the colon.

In a mouse model, colitis (inflammation of the colon) was chemically induced and then reduced by giving butyrate enemas. I wonder what a mouse enema looks like. Interestingly, there was a human study conducted in the Netherlands where butyrate enemas were given to patients with colitis. No improvement was noticed [10].

Given that butyrate has the potential to stimulate colon cell proliferation, this can have implications both for repair as well as for uncontrolled growth (cancer).

Since it seems like there is always somebody out there trying to cash in on the latest health craze, I searched for butyrate supplements. Keep in mind that butyrate taken orally wouldn’t make it to the colon. However, if the supplement is enterically coated it might or might not get there, but it would be a necessary prerequisite. It didn’t take long to find some products.

I can envision the day where boutique spas will spring up offering butyrate infusion services: Gisele Bundchen fecal transplants and butyrate enemas all the while sipping super-resistant starch smoothies, anyone? Take a few minutes to watch the video below are a great visualization of the gut microbiome and the action of butyrate, just try to overlook the narrator’s pronunciation of “intestine.”

Photo Credits (via Morguefile.com):

beans: lisasolonynko

colombo: Prawny

bran: dave

DNA: imelenchon

Gut Microbiome Link To Obesity

The topic of “gut bacteria” has hit the mainstream media like an outbreak of the Norwalk virus on a Paleo cruise ship. The headlines are screaming that bad gut bacteria are making us fat, insulin resistant and the cause behind metabolic syndrome. Likewise, we are hearing the panacea claims for cultivating good gut bacteria: weight loss, insulin and glucose normalization, reversal of type 2 diabetes, and more. This post will be geared towards those following a low-carb diet and will discuss the practical implications of gut microbiota with respect to weight loss and blood sugar control. A more thorough discussion of this topic can be found at the following reference [1].

The fact that human feces are made up of 55% bacteria (dry mass) should give one pause to reflect on this amazing fact prior to hitting the flush lever [2]. In fact, our lower intestinal tract is teeming with bacteria comprised of a wide variety of species. This is referred to as the gut microbiome, and thanks to modern DNA technology, is being mapped like the human genome [3].

The furor over good and bad gut bacteria comes from mice studies showing that mice implanted with feces from obese mice became obese. This was not the case with fecal specimens from lean donor mice [4]. The bacterial species vary in relative amounts with one type present in a lesser ratio in obese mice. This difference in bacterial ratios has also been found for humans [5]. For simplicity’s sake, we’ll call this either “lean bacteria profile” or “obese bacteria profile.”

Mouse and human studies also suggest that the bacteria profile can be altered through diet and exercise [6]. Simply put, the obese bacteria profile can be changed over time to a lean bacteria profile by a low fat/high plant polysaccharide diet. Likewise, a lean bacteria profile can be changed over time to an obese bacteria profile on a high fat/high sugar Western type diet [7]. In a human study, obese metabolic resistant men receiving a fecal transfer from lean donors didn’t lose weight, but did exhibit increased insulin sensitivity [8]. Despite these findings, I wouldn’t rush out just yet, and get a fecal transplant from a svelte supermodel.

It turns out, that obese bacterial forms that are increased relative to their lean counterparts are efficient at extracting energy from the undigested food matter entering the lower intestinal tract. This extracted energy in the form of short chain fatty acids (SCFA) can then be utilized by the host to pack on pounds [9].

Furthermore, there is speculation that the metabolic byproducts of these bacterial forms can negatively influence the host metabolism causing increases in lipogenesis in the liver, decreases in release of satiety peptides from the intestines, release of inflammatory factors into the bloodstream, just to name a few undesirable consequences. Parasites are notorious for influencing host behavior to ensure their survival and multiplication [10].

I think now would be a good time to take a deep breath. While we have some elegant studies, we’re still left with correlations and a lot of speculation. Always keep in mind that correlation does not necessarily equal causation, unless of course when it does.

Okay, so you’re thinking all I have to do is take a probiotic containing the good bacteria. However, I’ve been going through the contortions of using the term “obese bacteria profile” and “lean bacteria profile” for a reason.

It is the relative ratios of these bacterial types where the difference occurs, not the absolute numbers.

We are also dealing with an ecosystem as complex as a rainforest. And like a rainforest, the gut microbiome could be catastrophically upset by ham-fisted interventions like taking a probiotic. A cursory look at the probiotics on the market reveals that all contain bacteria in the obese profile category.

There is another important link between gut bacteria, obesity, metabolic syndrome, insulin resistance, high fat/high sugar diet and that is… wait for it… inflammation! Certain bacteria produce lipopolysaccharides that are recognized by the immune system resulting in a cascade of inflammatory reactions [11].

In an earlier post, I talked about berberine and its ability to control blood sugar and positively alter insulin signaling. There is some research to suggest that berberine influences the gut microbiome to shift it towards the lean bacterial profile [12]. Other things that have been suggested for changing the gut bacteria profile for the better are glutamine, green and black tea and some polyphenols [13, 14].

What about prebiotics? In other words, “Is there something I can feed my gut bacteria to induce a favorable ratio?”

Again, we’re dealing with a delicate balance. Just like fertilizer runoff into a lake can cause an undesirable algal bloom the situation may exist where it’s possible to “overfeed” the gut microbiota. This condition is apparent to those consuming high amounts of high-fiber foods and experience undesirable side effects. On the flip side, it may be possible to “underfeed.” One study of a high protein/very low-carb (20g) diet suggests negative consequences for gut microbiota and gut health in general [15] as a result of nutrient restriction. Prebiotics deserve their own scrutiny and will be covered in a future post

What about what not to feed your gut biota?

Many of those following a low-carb diet and dieters in general, consume some form of sweetener substitute as part of their regimen (Full Disclaimer: I despise the taste of all sugar substitutes and that includes stevia, sorry Rich). There are studies suggesting that things like aspartame can shift the bacteria profile to that of the obese type [16, 17]. Low carbers are also fond of coconut oil and tout it, among other things, as an antibacterial. What effect it might have, positive, negative or neutral on the gut bacteria profile? I have not seen any scholarly work in this area, but a whole lot of speculation in the blogosphere leans mostly towards the beneficial. There is evidence that saturated fat changes the gut profile for the worse [18].

No worries, Rob. We’ll just have to go our separate ways when it comes to stevia – I put that shizz on everything! I plan to do a series on sugar substitutes along with an in-depth post on stevia. I am interested in what effects it may have on gut bacteria.

The overarching concept that I took way from delving into this topic:

There is a constant and strong back and forth interaction between the gut and organ systems involved in energy production; e.g. liver, pancreas, visceral fat stores, hypothalamus, skeletal muscle.

This also holds for the immune system. If any disruption of these feedback loops occurs, it can set in motion a vicious cycle of obesity and insulin resistance. So you can’t expect to try to change your gut profile to a favorable one, yet continue to eat the proverbial Western diet, not exercise or change lifestyles that cause inflammation.

Maintaining a healthy gut profile should just be one of the several strategies as outlined here on PracticalCarbs.com.

Berberine Supplement Analysis

A subset of people interested in low-carb diets have issues with insulin resistance, high fasting blood glucose levels, and potentially type 2 diabetes. Berberine, a yellow compound occurring abundantly in some plants, has been drawing some attention in the low-carb blogosphere. This is due to both its folk use along with scientific research showing positive effects on insulin and glucose control. On a side note, my first encounter with berberine was while working as a researcher for the Department of Agriculture. We used it in the lab for histological work to stain cells.

This post will explore some of that research, along with availability and cautions regarding self-treatment with berberine. In addition, we’ll look at berberine in a head-to-head matchup with the popular prescription, glucose control medication, metformin.

At the outset, a cautionary note should be given to those operating under the, “Natural Supplement Product = Perfectly Safe and Superior to Big Pharma’s Pills” worldview. Berberine is available in its pure form as an over the counter (OTC) supplement. This type of potency is rarely seen in the supplement herb market where extracts are standardized to contain some fraction of the compound. Please see my post on the standardization of herbal supplements for more on this issue.

Furthermore, berberine is a benzylisoquinoline alkaloid. Morphine is also a benzylisoquinoline alkaloid. In fact, there is a host of natural and synthetic isoquinolines with potent pharmacological properties. As a result, berberine supplements have the potential to possess both the potency of a pharmaceutical as well as the potential towards toxicity.

The Chinese have a long-standing relationship with berberine. Berberine containing plants were mentioned in ancient Chinese texts over 2,000 years ago for the treatment of infections.

More recently in 1988, Chinese researchers noticed a beneficial effect on glucose parameters in diabetic patients given berberine for diarrhea. Since then, there has appeared quite a bit of research showing positive effects on glucose and insulin control. These studies run the gamut of experimental subjects and protocols: mice and rats, isolated cells all the way to human studies. The bulk of this research is coming from Chinese institutions and researchers [1].

Berberine has been proposed to work in a multitude of ways. Some mechanisms include:

Increases AMPK activity which has a variety of actions and requires its own posting [2,3].

Has a positive effect on beneficial gut bacteria, which is a subject that is worthy of its own post [8].

Metformin, the pharmaceutical agent used as a treatment option for type 2 diabetes, works in ways similar to berberine. Metformin isn’t all that far removed chemically from compounds built around the molecule, guanidine, found naturally in some plants. In fact, metformin consists of two guanidine molecules linked together.

One such plant is goat’s rue, which was used in the middle ages to treat diabetes. It was later found to contain guanidine compounds responsible for its glucose lowering properties. In fact, these plant compounds were found to be too toxic to use pharmaceutically for the treatment of type 2 diabetes, but led the way to metformin’s development [9].

In one study comparing metformin to berberine, it was found that both had similar beneficial effects on HbA1c, pre and post meal blood glucose, and insulin. However, it turned out that berberine had a greater beneficial effect on triglycerides and cholesterol [10].

Other human and mice studies support berberine’s effect on lipid profiles by reducing LDL (bad) cholesterol and triglycerides by up to 16 percent and 23 percent respectively [11,12].

What about cost of the two?

A post on berberine by Evelyn aka CarbSane on her blog quotes a month’s script for metformin at $4/month and compares it to Glycosolve, a supplement formula containing berberine, at $30/ month. Swanson Health Products sells generically labeled, berberine, at $10 for a month’s supply. I suspect one is paying in part for the fancy name (among other things) in the Glycosolve product.

However, there are some other differences–tangible and subtle–between metformin and berberine.

You will need a prescription and a doctor’s approval for metformin. This is not the case with berberine. I can walk down the street to my friendly retail supplement store and buy a bottle of pure berberine. This gives some empowerment to the individual with glucose issues, but also comes with added responsibility in the form of precautions.

Considering that berberine has statin-like qualities that metformin doesn’t appear to have, it could provide a potential benefit to those having to take metformin in addition to a statin as statins come with added costs and side effects. The typical dose of berberine is 500 mg before each meal. I suspect there will be products in the future that claim better absorption properties since berberine has poor oral bioavailability [13].

I’m certainly not advocating that you rush out and load up on berberine, quite the contrary. As mentioned earlier, prescription version or OTC, berberine is still a powerful substance with definite effects on your endocrine system. It’s in your best interest to discuss the possible use of berberine with your doctor. Perhaps more conservative means can be tried first to control blood glucose such as diet and activity modifications. A graduated protocol beginning with very conservative treatments and only progressing to more aggressive ones when necessary is almost always the best approach when it comes to your health. Taking a drug – prescription or natural – is no exception.

Photo Credits (morguefile.com):

Berberine Bottle: Rob Rojas (not morguefile.com)

Chinese Writing on Rock/Guilin, China: SamHakes

Blood Sampling: cohdra

Pharmacy: calgrin

Statue with Scale: southernfried

Creating Resistant Starch in the Kitchen

Resistant starches (RS) seem to have appeared out of nowhere in the popular press along with a lot of fanfare about their health benefits. Resistant starches are nothing new, as they’re found to some degree in all plants. Starch is the plant kingdom’s storage form of glucose and is analogous to glycogen in the animal kingdom. That is why, when digested into glucose, it can lead to the insulin spikes that low-carbers are so eager to avoid.

Resistant starches on the other hand, are forms of the starch that cannot be broken down by the starch-digesting enzyme, amylase, and converted into glucose. Resistant starches, however, can be used by beneficial colon bacteria as an energy source. You can think of RS as fuel for gut bacteria.

Amidst the recent hype on resistant starches, some temperance is in order. Resistant starch consumption may be contraindicated for those with certain digestive disorders such as celiac disease, gluten intolerance, small intestinal bacteria overgrowth, and IBS, to just name a few. Furthermore, the reduction in caloric content may be minimal since the fat substances produced by the gut bacteria can be absorbed and burned as calories, which sort of defeats the purpose [1].

There are actually four types of resistant starches, appropriately named: RS1, RS2, RS3 and RS4. We will focus on only one type here: RS3.

Kitchen Chemistry

Type RS3 is formed by cooking the starch source in water and then allowing it to cool. If you’re so inclined, this provides the unique opportunity to take on the role of playing chemist in the kitchen. It also empowers the low-carb dieter to somewhat reduce the glycemic load of a once in a while pasta, bean, potato or rice dish.

Without going into too much messy scientific detail, when heated in water the two components of starch, amylose and amylopectin, form a gel, that when cooled, realign in a process known as retrogradation. This process turns the starch components into a crystalline form that is resistant to the actions of amylase. It may require several days in the fridge for this transformation to be completed.

It’s all in the cooling

Again, some reservation needs to be applied here. While the resistant starch levels are increased by this process, it might turn out to be only a small portion of the digestible starch. The original very high glycemic index of the starch may be significantly reduced, but it may still wind up being in the high range. Again, how this affects you all depends on your personal tolerance for high GI carbohydrates.

Getting back to our kitchen chemistry experiment, as a test case, I want to focus on maximizing RS3 in a potato salad preparation:

First we’re going to select the small red potato variety since they hold up well to boiling and are low in starch. There is some research to show that cooking the starch with an oil increases RS3 [2].

Lower GI Potato Salad Recipe

Ingredients:

4 Red Potatoes

8 Tbsp EVOO

2 Tbsp Apple Cider Vinegar

Fresh Rosemary

Salt, Pepper and Oregano to taste

Directions:

Bring large pot of water to a boil

Add red potatoes boiling water along with 2 Tbsp EVOO. Boil until soft.

*The addition of vinegar to cooled potatoes was found to further decrease the GI index in one study.
**Rosemary has been implicated in lowering the GI of meals.

The long cooling time for the potatoes is because red potatoes are high in amylopectin, and take longer to undergo the retrogradation process than amylose [3].

I use an empty Claussen’s sauerkraut jar to store the potato salad. One study found that boiled potatoes stored in the cold for a day reduced the GI of the potatoes by 43%, however, the GI went from a whopping 168 to a still very high 96. Only the abstract was available, and no mention was made to the type of potato used. An even greater reduction in GI may have been achieved if the potatoes were allowed to cool for a longer period [4].

In the immortal words of the late, great, Julia Child, “Bon appetit!”

Thanks for this post on a timely topic, Rob. I’ve been noticing quite a bit of discussion on RS on some of the low-carb and Paleo blogs. I’m more interested in its effects on gut flora from a prebiotic standpoint rather than as a technique to lower GI. I’m not much of a potato eater, though we enjoy a cool, refreshing potato salad during the summer months. Perhaps you can write a follow up post on gut flora and the basics of pre and probitoics. Here’s an article that appeared in the Washington Post after you wrote this about using the same technique with rice. -Rich

The Green Coffee Bean Extract Study and Misleading Research

As a reader of this blog you are probably interested in maintaining a healthy weight by following an eating plan that’s appropriate for your metabolic type, exercising intelligently, and if beneficial, bolstering your efforts with a little help from nutritional supplements. You want information that is based on sound principles of scientific research for all of these things, especially when it comes to nutritional supplements.

But how can you know that a health benefit claim of a supplement manufacturer is legitimate or not? After all, no one wants to waste their hard-earned money on products that don’t work as claimed or worse, are potentially dangerous. Let’s explore the issue of evaluating supplement research and claims for scientific validity by examining a very popular and highly-touted weight loss supplement: Green coffee bean extract (GCBE).

GCBE is an extract that is made from unroasted coffee beans. Coffee beans are naturally green in color prior to the roasting process. A cup of Joe made from green coffee beans would taste terrible as you might imagine. The active ingredient in GCBE is thought to be chlorogenic acid. The product we’ll examine is standardized to contain 46% chlorogenic acid.

In The Land of Oz

The GCBE craze started when America’s favorite TV doctor, Dr. Oz, promoted GCBE on his show as the new miracle weight loss supplement.

He waxed eloquently about a study presented before the largest scientific society (American Chemical Society) that yielded a 17 lb. weight loss in 12 weeks and a16% reduction in total body fat all while consuming a 2400 calorie diet. And ready for this? All without any exercise! Where do I put my credit card info?

There was only one problem: the research was heavily flawed and Dr. Oz should have at least taken the time to evaluate it before making such fantastic claims. He remained steadfast, however, in these claims even when called before a Congressional hearing on weight loss supplements.

The first question that should always be asked about any study, regardless of its claims, is who sponsored the research? This little detail is vital when it comes to sniffing out any potential bias resulting from a vested financial interest based upon the outcome of the study whether it be positive, negative or neutral.

In the 1950s with increasing evidence that cigarette smoking caused lung cancer the tobacco giant, Phillip Morris, created an entity known as the Tobacco Institute Research Committee (TIRC) to sponsor research into this supposed link. PM hired a cancer researcher who believed cancer was entirely due to genetics and not to any extraneous factors such as harmless cigarette smoke. Research was funded with this biased focus. Needless to say no relevant data came out of this research [1].

The research for GCE was sponsored by a supplement company in Austin, TX, the maker of the GCBE evaluated in the study. This doesn’t automatically mean the study is flawed scientifically. It’s just a red flag that must be evaluated along with the rest of the methodologies employed in the study. Appropriate credit should be given to any supplement manufacturer that goes through the expense and trouble of sponsoring a legitimate scientific study of their product to show efficacy and safety.

Next, we need to consider where the study was conducted. Was it conducted at an institution that has integrity and reputation for quality scientific research? The GCE was conducted at the Health Sciences Clinic in Bangalore, India. While the name Health Sciences Clinic sounds impressive, an Internet search came up empty.

What about the researchers themselves? Are they recognized leaders in this field? The paper lists three authors: Joe A Vinson, Bryan R Burnham, and Mysore V Nagendran. Typically, the first author named is the lead scientist and has the most time invested in the study followed by the second author. The last author is usually the person in whose lab the study was conducted in.

Both Vinson and Burham are located at the University of Scranton in Pennsylvania; a small private Catholic and Jesuit school. Vinson is in the chemistry department. His homepage on the University’s website is a long rambling read that has very little to with his science background. In fact, I don’t think I’ve seen anything quite as bizarre for an academic’s homepage. He provides such interesting tidbits such as to how his mother went to high school with Pretty Boy Floyd and in his first play of his burgeoning amateur acting career; he was cast as the Fireman in Eugene Ionesco’s absurdist comedy The Bald Soprano. Said fireman goes around in pink long underwear putting out fires. A noble endeavor indeed, but how this is relevant to Vinson’s qualifications as a scientist seem tangential at best. (http://www.scranton.edu/faculty/vinson/). Burham is in the psychology department. A Google search of Nagendran turns up empty other than mentions of this study.

Another consideration is where were the results published? Prestigious journals like Science and Nature would really cause one to sit up and take notice. This study was posted in the journal Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. As impressive as this may sound, it turns out that the publication is an open access journal as opposed to a subscription-only journal.

Open access journals are a product of the Internet age. They enjoy the advantage of anyone being able to view the entire article without paying a fee with the attendant disadvantage (or advantage depending on which side you’re on) of potentially undermining the peer review process, which is vital to any sound research study. Some publishers will just accept a fee from the authors without adequate peer review. In fact, a staff writer for Science critical of these journals submitted a deliberately flawed study that in many cases was accepted to these types of journals. There are a few solid open-access publishers. The publisher of this particular journal is not one of them.

The house of cards the GCBE study was based on is beginning to come into focus at this point. Let’s now have a look at the study itself. You’ll hear Dr. Oz and his ilk spouting. “In a randomized, double-blind, placebo controlled study” to get you really juiced up about all the science behind the product they’re pushing. Yes, this is important, but neither the research subjects nor the persons conducting the study should know who is getting the supplement in order to satisfy the double-blind claim. In the case of this study, that would be knowing which subjects received the GCBE or a placebo pill containing no GCBE. Problems with this particular study can be discovered early on by simply reading the Materials section of the published report.

First of all, the study involved a small number of people: 16. This is an extremely small sample size and whatever statistically significant data can be derived from it is highly questionable. The subjects were then divided into three groups and all were given a high dose of GCBE for 6 weeks, low dose GCBE for 6 weeks, and a placebo for six weeks. There was a two week period between each treatment when nothing was administered.

The only difference between these three groups is the order in which they were administered the three different treatments. A crucial control group is missing: a group that got only the placebo throughout the study. The other problem is the high dose and the low dose treatments were readily apparent to both the research subject and the researcher since only two pills were taken per day for the low dose segment and three pills for the high dose segment. All groups lost weight in the initial six weeks of the study, even in the placebo group [2].

The 8 kg or 16 lb. lost after 22 weeks of the study is deceiving, and the data would suggest it had more to do with the daily monitoring of their diet [3]. If we look at the data for the high dose GCBE, it would be a more modest 2 kg or 4 lb. of weight lost after 22 weeks.

In summary a study should be designed to:

Have adequate controls in place to eliminate results that are due to other factors. Admittedly, controls can become unwieldy especially in human studies. In this case, it would appear the effects of the study were more due to the daily monitoring of the subjects’ diet. The missing control group of receiving only placebo throughout the study would have flushed this out.

Be double-blinded which means neither the researcher nor the subjects should know who is getting the supplement or a placebo until the end of the experiment.

Be randomized which means that the subjects are randomly selected for each treatment group. There is something suspicious in this study since one of the treatment groups starts the trial at a considerably lower mean weight.

Have an adequate sample size so statistically significant results can be reported with confidence.

It turns out that initially the paper was submitted to a journal that had some integrity but they rejected it for publication. It was only then that Vinson and Burham were recruited by the supplement company to lend their scientific gravitas as well as to rework the paper. While they noticed discrepancies and asked for clarification from India, they never reviewed the raw data or questioned the changed numbers.

The FTC then got involved and demanded to see the data and found that the Indian researcher had in some cases changed the final weights and even the duration of the study. Vinson and Burham caught “green-handed” had no choice but to send a retraction to the journal. The FTC fined the supplement company 3.5 million dollars.

The FTC deserves a great deal of credit going after these fraudsters. Obviously, some reforms need to be implemented by the supplement industry to protect the consumer against false claims. The FTC has suggested requiring two independent studies be conducted before claims can be made. I would suggest some method to provide more separation between the supplement companies and the researchers. Another added protection is to force the supplement companies to submit the trial parameters to clinicaltrials.gov before the start of the study so it can’t be altered after the fact [4]. Sometimes, government regulation is a necessary evil. The alternative is to let the wolves to roam free to prey on the unsuspecting and defenseless.

Standardized Herbal Supplements – Digging Beyond Percentages

I’m delighted to welcome Rob Rojas as an occasional contributor to the PracticalCarbs.com blog. He’s chosen as his first topic the vexing issue of standardization for herbal supplements. He’s covered this issue previously on his own blog and expands upon it further here. Warning: contains some mild chemistry lingo along with some very basic math. -Rich Rojas

The greatest advance in the herbal supplements industry has been the introduction of standardized products to the consumer and researcher. The standardization process brings herbal supplements more in line with prescription medicines in terms of potency and consistency. In short, these products typically contain plant material that has been extracted in such a manner as to concentrate the active ingredient(s) to a specific concentration, which in turn, requires verification by various analytical methods.

While great for the consumer, it can be a daunting undertaking when navigating the aisles of your favorite retail store or browsing nutritional supplement sites online. This is because there are often a variety of standardized products for a single herbal product. By way of example, I’d like to take you along with me as I have a look at a one specific herb (Turmeric) and the various products for sale containing it in one particular store near where I live. I think it will be enlightening.

Turmeric is known for its anti-inflammatory properties. It’s also been getting its fair share of press recently for its possible roles in preventing the development of Alzheimer’s disease and for use as an antidepressant. It also happens to have one of the widest selections of standardized forms of all the herbal products in the store that I checked, so a great one to start our investigation with. The active part of turmeric is thought to reside in a class of compounds called curcuminoids and this is what we’ll focus on.

A Dizzying Array of Options

First, we’ll head towards the end of the ‘T’ section, where just beyond the Turkey Tail Mushroom bottles, we encounter our quarry. The first specimen is a Full Spectrum Turmeric with a rather generic looking black and white label. The term Full Spectrum kills me. It’s akin to calling a burrito a “wrap.” In reality it’s just the unprocessed, ground-up turmeric root stuffed into 00-size gelatin capsules. Yes, the same stuff that is in the turmeric spice jar from the supermarket. I reflexively smack my head and then look around to see if anyone was looking.

You can actually see the presence the curcuminoids in the raw spice. They’re responsible for the characteristic yellow-orange color and annoying stains. Typically, the raw spice has 3.14% by weight, curcumin, which is its major curcuminoid. A bottle of 240 capsules of 720 mg each costs a whopping $1.99 which comes out to less than a penny per capsule. Going by the 3.14% by weight figure, one capsule should contain about 22.6 mg curcumin (720mg x 0.0314). But this is mere conjecture, since there is no standardization. Not that the raw spice couldn’t be standardized. It would require that it be tested in the lab for curcumin content and then state on the label the percentage of concentration.

Sticker Shock

We next come upon a product labeled “Turmeric Phytosome with Meriva.” The first thing that jumps out is a fancier label which dollars-to-donuts is probably going to mean a higher sticker price. Looking at the back-of-the-bottle label, we find that it is an extract standardized to contain 18%-22% curcuminoids. Note that this is not specific for any one curcuminoid, but if we assume the majority is curcumin, this would be about a 67% increase in curcumin content over the raw unprocessed product. Each 500 mg capsule would contain 110 mg curcumin (500 mg x 0.22). Just like the carat system in gold pricing, the higher the curcumin content, the higher the price. It turns out sixty 500mg capsules cost $10.99.

A bit further down, we find ourselves in the high-rent district. A product labeled “Curcumin Complex” presents itself and the back label shows it is standardized to contain a whopping 95% curcuminoids. But wait, there’s a further breakdown: 73-83% Curcumin, 14-24% Desmethoxy Curcumin and 2-4% Bisdemethoxy Curcumin. For this type of breakdown, a more sophisticated analysis must have been required than the previous product, which along with increased curcumin content, is reflected in the price: $17.99 for sixty capsules. Doing the math, we would expect each 875 mg capsule to contain 682 mg curcumin (875 mg x 0.78).

So far things have progressed as one would expect: move down the line of products and one goes from raw (unprocessed-unstandardized) product of approximately 3.14% to 18-22% and then to 73-78% standardized curcumin. The price increases from 2, 11 to 18 dollars a bottle respectively. However, there are two other products lurking in the hinterlands before getting to the Uva Ursi that aren’t following the pattern of increasing curcuminoid content. It’s tough to do much better than 95% curcuminoids.

What Your Body Can’t Absorb is Money Down The Drain (Literally)

The products on the outskirts attempt to address a problem with curcuminoids: due to their low solubility in water, they’re not readily absorbed. All that effort by the manufacturer to come up with a product containing 95% curcuminoids in the end offers little benefit to the consumer if only a fraction is capable of being absorbed. That’s why the previous standardized products had either Bioperine or was prepared as a Phytosome. Both formulations attempt to overcome the absorption problem.

These last two outliers are “Advanced Tetrahydro-Curcuminoids” and “Theracurmin.” Advanced Tetrahydro-Curcuminoids is standardized to contain 95% tetrahydrocurcuminoids, which are hydrogenated curcuminoids and theoretically more bioavailable. The cost is $14.99 for sixty 200 mg capsules. Finally, Theramin would seem like an anomaly standardized to a mere 8.5% curcumin and the most expensive at thirty 300 mg capsules for $14.99, however, it’s in a colloidal form which again tries to deal with the low absorption problem.

Hopefully, this little adventure will have begun the discussion of the challenges of standardizing herbal supplements and the attendant confusion it generates for the consumer. Though we just focused on turmeric here, the variations in both contents, concentration of the active ingredient, and perhaps most importantly, the ability of the human body to absorb it, extend to most other herbs. We’ll have ample opportunity to explore these issues with more of the popular herbal supplements in future posts, so please stay tuned!